Attention Deficit Disorder (ADD), a commonly diagnosed nervous system illness in children, is often treated with methylphenidate hydrochloride. Methylphenidate is sold in commerce under the name Ritalin®. Ritalin is a registered trademark owned by Novartis Corporation.
Symptoms of ADD include distractibility and impulsivity. A related disorder, termed Attention Deficit Hyperactivity Disorder (ADHD), is further characterized by symptoms of hyperactivity, and is also treated with methylphenidate hydrochloride. Methylphenidate drugs have also been used to treat cognitive decline in patients with Acquired Immunodeficiency Syndrome (AIDS) or AIDS related conditions. See, e.g., Brown, G., Intl. J. Psych. Med. 25(1): 21–37 (1995); Holmes et al., J. Clin. Psychiatry 50:5–8 (1989). These various treatment regimes comprise administering to the patient one or more oral doses of a methylphenidate drug such as methylphenidate hydrochloride.
Methylphenidate exists as four separate optical isomers. These four optical isomers are shown below.
Pharmaceutically acceptable salts of Methylphenidate, the hydrochloride for example, are sometimes administered clinically.
Clinically, the threo pair of enantiomers of methylphenidate hydrochloride is generally administered for the treatment of ADD and ADHD. The hydrochloride salt is commonly referred to simply as “methylphenidate”. Unless indicated otherwise, the term “Methylphenidate” is used broadly herein to include methylphenidate and pharmaceutically acceptable salts thereof, including methylphenidate hydrochloride.
The threo racemate (pair of enantiomers) of Methylphenidate is a mild central nervous system stimulant with pharmacological activity qualitatively similar to that of amphetamines. Undesirable side effects associated with the use of the dl-threo racemate of Methylphenidate include anorexia, weight loss, insomnia, dizziness and dysphoria. Furthermore, the racemate, which is a Schedule II controlled substance, produces a euphoric effect when administered intravenously or through inhalation or ingestion, and thus carries a high potential for abuse.
It is known in the art that the pharmacodynamic activity of dl-threo-methylphenidate resides in the d-threo isomer (Clin. Pharmacol. Ther., 52:561–568 (1992)). Therefore, while di-threo-methylphenidate is generally used therapeutically, this racemate includes the l-isomer which apparently makes no significant contribution to the pharmacological effectiveness of the drug, but likely contributes to the associated side effects. It is thus desirable to administer only the active d-threo form of the drug.